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4inb

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==Crystal Structure of the N-Terminal Domain of HIV-1 Capsid in Complex With benzodiazepine Inhibitor==
==Crystal Structure of the N-Terminal Domain of HIV-1 Capsid in Complex With benzodiazepine Inhibitor==
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<StructureSection load='4inb' size='340' side='right' caption='[[4inb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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<StructureSection load='4inb' size='340' side='right'caption='[[4inb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4inb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4INB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4INB FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4inb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4INB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4INB FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1F6:(3Z)-3-{[(2-METHOXYETHYL)AMINO]METHYLIDENE}-1-METHYL-5-PHENYL-7-(TRIFLUOROMETHYL)-1H-1,5-BENZODIAZEPINE-2,4(3H,5H)-DIONE'>1F6</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e91|4e91]], [[4e92|4e92]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1F6:(3Z)-3-{[(2-METHOXYETHYL)AMINO]METHYLIDENE}-1-METHYL-5-PHENYL-7-(TRIFLUOROMETHYL)-1H-1,5-BENZODIAZEPINE-2,4(3H,5H)-DIONE'>1F6</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4inb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4inb OCA], [https://pdbe.org/4inb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4inb RCSB], [https://www.ebi.ac.uk/pdbsum/4inb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4inb ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4inb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4inb OCA], [http://pdbe.org/4inb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4inb RCSB], [http://www.ebi.ac.uk/pdbsum/4inb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4inb ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/Q79791_9HIV1 Q79791_9HIV1]] Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex (By similarity).[SAAS:SAAS000071_004_008806] Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers (By similarity).[SAAS:SAAS000071_004_011858]
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[https://www.uniprot.org/uniprot/A9PKC6_9HIV1 A9PKC6_9HIV1]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The emergence of resistance to existing classes of antiretroviral drugs underlines the need to find novel human immunodeficiency virus (HIV)-1 targets for drug discovery. The viral capsid protein (CA) represents one such potential target. Recently, a series of benzodiazepine inhibitors was identified via high-throughput screening using an in vitro capsid assembly assay (CAA). Here, we demonstrate how a combination of NMR and X-ray co-crystallography allowed for the rapid characterization of the early hits from this inhibitor series. Ligand-based (19) F NMR was used to confirm inhibitor binding specificity and reversibility as well as to identify the N-terminal domain of the capsid (CA(NTD) ) as its molecular target. Protein-based NMR ((1) H and (15) N chemical shift perturbation analysis) identified key residues within the CA(NTD) involved in inhibitor binding, while X-ray co-crystallography confirmed the inhibitor binding site and its binding mode. Based on these results, two conformationally restricted cyclic inhibitors were designed to further validate the possible binding modes. These studies were crucial to early hit confirmation and subsequent lead optimization.
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Monitoring Binding of HIV-1 Capsid Assembly Inhibitors Using (19) F Ligand-and (15) N Protein-Based NMR and X-ray Crystallography: Early Hit Validation of a Benzodiazepine Series.,Goudreau N, Coulombe R, Faucher AM, Grand-Maitre C, Lacoste JE, Lemke CT, Malenfant E, Bousquet Y, Fader L, Simoneau B, Mercier JF, Titolo S, Mason SW ChemMedChem. 2013 Mar;8(3):405-14. doi: 10.1002/cmdc.201200580. Epub 2013 Feb 10. PMID:23401268<ref>PMID:23401268</ref>
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==See Also==
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*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4inb" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Coulombe, R]]
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[[Category: Human immunodeficiency virus 1]]
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[[Category: Capsid]]
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[[Category: Large Structures]]
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[[Category: Structural protein]]
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[[Category: Coulombe R]]
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[[Category: Viral protein]]
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[[Category: Viral protein-viral protein inhibitor complex]]
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Current revision

Crystal Structure of the N-Terminal Domain of HIV-1 Capsid in Complex With benzodiazepine Inhibitor

PDB ID 4inb

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